CAJ | 학술논문

喜树碱/衍生物%羟基喜树碱%抗纤维化药物/用法,剂量%青光眼/手术,药物疗法%高眼压%组织病理学技术/苏木精-伊红染色,Masson三重染色%小梁切除术/滤过泡%动物模型喜樹堿/衍生物%羥基喜樹堿%抗纖維化藥物/用法,劑量%青光眼/手術,藥物療法%高眼壓%組織病理學技術/囌木精-伊紅染色,Masson三重染色%小樑切除術/濾過泡%動物模型
희수감/연생물%간기희수감%항섬유화약물/용법,제량%청광안/수술,약물요법%고안압%조직병이학기술/소목정-이홍염색,Masson삼중염색%소량절제술/려과포%동물모형
Camptothecin/analogs and derivatives%Hydroxycamptothecin%Anti-fibrosis agents/administration and dosage%Glaucoma/surgery,drug therapy%Ocular hypertension%Histological technique/hematoxylin-eosin staining and Masson trichrome staining%Trabeculectomy

背景眼外滤过手术一直是治疗青光眼的主要术式,而其术后滤过道瘢痕化是导致青光眼手术失败的主要原因.寻找有效和安全的抗瘢痕药物是抗青光眼滤过手术的研究热点. 目的探讨羟基喜树碱(HCPT)在小梁切除术中的应用,评价HCPT对结膜下滤过泡的抗增生作用及其最佳剂量. 方法 12 ～16周龄健康新西兰大白兔40只制作抗青光眼滤过手术模型,采用随机数字表法将动物随机分为生理盐水组、丝裂霉素C(MMC)组、0.3 g/L HCPT组及1.0 g/L HCPT组,每组10只,均取右眼行常规小梁切除术,术中在不同组兔眼巩膜表面及巩膜瓣下分别放置含生理盐水、0.3 g/L MMC、0.3 g/L HCPT及1.0 g/L HCPT的棉片5 min.于术后1、4、7、14、21、28 d用Icare眼压计测量眼压；裂隙灯显微镜下观察术眼滤过泡情况以评价各种药物的疗效,球结膜、角膜、前房炎症反应、虹膜周边切口及晶状体混浊情况,加前置镜后观察视网膜情况,以评估药物不良反应.于术后7、14、28 d分别处死3、3、4只动物,取术眼5 mm×5 mm手术区组织,包括球结膜、结膜下组织及巩膜,分别行苏木精-伊红染色及Masson三重染色,比较各种药物的抗纤维组织增生效果.采用Kaplan-Meier分析比较各组兔术眼功能性滤过泡的生存时间.结果各组间实验兔术眼的眼压随着时间的变化明显不同,差异均有统计学意义(F分组=20.79,P=0.00;F时间=85.34,P=0.00；F交互作用=2.13,P=0.01),其中MMC组和1.0 g/L HCPT组术眼术后各时间点的眼压值均明显低于术前,差异均有统计学意义(P＜0.05),生理盐水组和0.3 g/L HCPT组仅能分别维持低眼压至术后第7天和第14天.术后生理盐水组、MMC组、0.3 g/L HCPT组及1.0 g/L HCPT组术眼滤过泡存活时间分别为(11.3±2.8)、(19.5±2.4)、(13.3±2.2)和(20.2±4.5)d,差异有统计学意义(log rank=11.92,P＜0.01),1.0 g/L HCPT组术眼滤过泡存活时间较其他组明显延长.术后7d内,各组术眼滤过泡面积和高度分级的差异均无统计学意义(P＞0.05),而术后7、14、28 d,生理盐水组和0.3 g/L HCPT组较1.0 g/L HCPT组与MMC组的滤过泡面积明显减小,差异均有统计学意义(P＜0.05).苏木精-伊红染色和Masson染色表明,MMC组与1.0 g/L HCPT组术区组织中炎性细胞明显减少,结膜下组织中纤维细胞增生量下降,胶原纤维染色减少. 结论小梁切除术中局部应用1.0 g/LHCPT能抑制术区组织的炎症反应和胶原纤维的增生,有效降低眼压,且功能性滤过泡维持时间长. 揹景眼外濾過手術一直是治療青光眼的主要術式,而其術後濾過道瘢痕化是導緻青光眼手術失敗的主要原因.尋找有效和安全的抗瘢痕藥物是抗青光眼濾過手術的研究熱點. 目的探討羥基喜樹堿(HCPT)在小樑切除術中的應用,評價HCPT對結膜下濾過泡的抗增生作用及其最佳劑量. 方法 12 ～16週齡健康新西蘭大白兔40隻製作抗青光眼濾過手術模型,採用隨機數字錶法將動物隨機分為生理鹽水組、絲裂黴素C(MMC)組、0.3 g/L HCPT組及1.0 g/L HCPT組,每組10隻,均取右眼行常規小樑切除術,術中在不同組兔眼鞏膜錶麵及鞏膜瓣下分彆放置含生理鹽水、0.3 g/L MMC、0.3 g/L HCPT及1.0 g/L HCPT的棉片5 min.于術後1、4、7、14、21、28 d用Icare眼壓計測量眼壓；裂隙燈顯微鏡下觀察術眼濾過泡情況以評價各種藥物的療效,毬結膜、角膜、前房炎癥反應、虹膜週邊切口及晶狀體混濁情況,加前置鏡後觀察視網膜情況,以評估藥物不良反應.于術後7、14、28 d分彆處死3、3、4隻動物,取術眼5 mm×5 mm手術區組織,包括毬結膜、結膜下組織及鞏膜,分彆行囌木精-伊紅染色及Masson三重染色,比較各種藥物的抗纖維組織增生效果.採用Kaplan-Meier分析比較各組兔術眼功能性濾過泡的生存時間.結果各組間實驗兔術眼的眼壓隨著時間的變化明顯不同,差異均有統計學意義(F分組=20.79,P=0.00;F時間=85.34,P=0.00；F交互作用=2.13,P=0.01),其中MMC組和1.0 g/L HCPT組術眼術後各時間點的眼壓值均明顯低于術前,差異均有統計學意義(P＜0.05),生理鹽水組和0.3 g/L HCPT組僅能分彆維持低眼壓至術後第7天和第14天.術後生理鹽水組、MMC組、0.3 g/L HCPT組及1.0 g/L HCPT組術眼濾過泡存活時間分彆為(11.3±2.8)、(19.5±2.4)、(13.3±2.2)和(20.2±4.5)d,差異有統計學意義(log rank=11.92,P＜0.01),1.0 g/L HCPT組術眼濾過泡存活時間較其他組明顯延長.術後7d內,各組術眼濾過泡麵積和高度分級的差異均無統計學意義(P＞0.05),而術後7、14、28 d,生理鹽水組和0.3 g/L HCPT組較1.0 g/L HCPT組與MMC組的濾過泡麵積明顯減小,差異均有統計學意義(P＜0.05).囌木精-伊紅染色和Masson染色錶明,MMC組與1.0 g/L HCPT組術區組織中炎性細胞明顯減少,結膜下組織中纖維細胞增生量下降,膠原纖維染色減少. 結論小樑切除術中跼部應用1.0 g/LHCPT能抑製術區組織的炎癥反應和膠原纖維的增生,有效降低眼壓,且功能性濾過泡維持時間長.
배경 안외려과수술일직시치료청광안적주요술식,이기술후려과도반흔화시도치청광안수술실패적주요원인.심조유효화안전적항반흔약물시항청광안려과수술적연구열점. 목적 탐토간기희수감(HCPT)재소량절제술중적응용,평개HCPT대결막하려과포적항증생작용급기최가제량. 방법 12 ～16주령건강신서란대백토40지제작항청광안려과수술모형,채용수궤수자표법장동물수궤분위생리염수조、사렬매소C(MMC)조、0.3 g/L HCPT조급1.0 g/L HCPT조,매조10지,균취우안행상규소량절제술,술중재불동조토안공막표면급공막판하분별방치함생리염수、0.3 g/L MMC、0.3 g/L HCPT급1.0 g/L HCPT적면편5 min.우술후1、4、7、14、21、28 d용Icare안압계측량안압；렬극등현미경하관찰술안려과포정황이평개각충약물적료효,구결막、각막、전방염증반응、홍막주변절구급정상체혼탁정황,가전치경후관찰시망막정황,이평고약물불량반응.우술후7、14、28 d분별처사3、3、4지동물,취술안5 mm×5 mm수술구조직,포괄구결막、결막하조직급공막,분별행소목정-이홍염색급Masson삼중염색,비교각충약물적항섬유조직증생효과.채용Kaplan-Meier분석비교각조토술안공능성려과포적생존시간.결과각조간실험토술안적안압수착시간적변화명현불동,차이균유통계학의의(F분조=20.79,P=0.00;F시간=85.34,P=0.00；F교호작용=2.13,P=0.01),기중MMC조화1.0 g/L HCPT조술안술후각시간점적안압치균명현저우술전,차이균유통계학의의(P＜0.05),생리염수조화0.3 g/L HCPT조부능분별유지저안압지술후제7천화제14천.술후생리염수조、MMC조、0.3 g/L HCPT조급1.0 g/L HCPT조술안려과포존활시간분별위(11.3±2.8)、(19.5±2.4)、(13.3±2.2)화(20.2±4.5)d,차이유통계학의의(log rank=11.92,P＜0.01),1.0 g/L HCPT조술안려과포존활시간교기타조명현연장.술후7d내,각조술안려과포면적화고도분급적차이균무통계학의의(P＞0.05),이술후7、14、28 d,생리염수조화0.3 g/L HCPT조교1.0 g/L HCPT조여MMC조적려과포면적명현감소,차이균유통계학의의(P＜0.05).소목정-이홍염색화Masson염색표명,MMC조여1.0 g/L HCPT조술구조직중염성세포명현감소,결막하조직중섬유세포증생량하강,효원섬유염색감소. 결론 소량절제술중국부응용1.0 g/LHCPT능억제술구조직적염증반응화효원섬유적증생,유효강저안압,차공능성려과포유지시간장.
Background The filtration surgery is the main method of treating glaucoma,which usually fails due to postoperative scarring.The study about application of anti-scarring agents in filtration surgery is a hotspot.Objective This study was to investigate whether topical administration of hydroxycamptothecin (HCPT) could be used to prevent postoperative scarring in after experimental glaucoma filtration surgery,and explore its optimal dose.Metbods Trabeculectomy was performed on the right eyes of 40 New Zealand white rabbits to establish the trabeculectomy animal models.The rabbits were then randomized into normal saline solution group,0.3 g/L mitomycin C(MMC) group,0.3 g/L HCPT group and 1.0 g/L HCPT group based on the intraoperative topical drugs using randomized number table method.The different drugs above-mentioned were put beneath the conjunctival flap and scleral flap for 5 minutes during the surgery.The intraocular pressure (IOP) was measured before and day 1,4,7,14,21 and 28 after the surgery with Icare tonometer,and the filtering area and height were measured under the slit lamp microscope to assess the efficacy of various drugs.The adverse effects were evaluated by examining the responses of the ocular anterior segment and retinal change.The specimens at operative zone were obtained in 7,14 and 28 days after surgery with the size 5 mm×5 mm for the hematoxylin-eosin staining and Masson trichrome staining to estimate the anti-fibrosis effect of various drugs,and to evaluate the survival time of functional bleb.Kaplan-Meier analysis was used to compare the survival time of functional bleb of different groups.The use and care of the animals complied with the Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Committee.Results The IOP was significantly different in the rabbits from different groups among various time points (Fgroup =20.79,P =0.00 ; Ftime =85.34,P =0.00 ; Fiion =2.13,P =0.01).From 1 day through 28 days after operation,the IOPs in MMC group and 1.0 g/L HCPT group were significantly lower than those before operation (all at P＜0.05).The survival time of functional bleb of different groups was (11.3 ±2.8),(19.5 ±2.4),(13.3 ±2.2) and (20.2 ± 4.5) days,respectively,showing a significant difference (log rank =11.92,P ＜ 0.01),with a considerable prolong in the 1.0 g/L HCPT group.No significant change was found in the bleb area and height among the four groups within 7 days after operation,but postoperative 7,14,28 days,the area and height values of bleb were significantly smaller in the normal saline solution group and 0.3 g/L HCPT group compared with the MMC group and 1.0 g/L HCPT group (all at P ＜ 0.05).Histopathological examination showed loosen subconjunctival tissue,less inflammatory cells and weaker collagenous fibrillary staining in the MMC group and 1.0 g/L HCPT group in comparison with the normal saline solution group and 0.3 g/L HCPT group.Conclusions The topical administration of 1.0 g/L HCPT inhibit the inflammatory response and collagen fibrosis and therefore prolong the survival time of functional bleb after glaucomatous filtering surgery.